ABSTRACT National survey data show that college students are at high risk for e-cigarette and polysubstance use. E- cigarette use patterns and associated effects are not well understood because existing statistical methods can only handle conventional EMA data and there is no well-validated consumption measure. This study will address these major challenges by pursuing the following specific aims: 1) Develop and disseminate statistical methodology and free software to analyze complex EMA data; 2) Conduct a longitudinal EMA study with the measurement burst design on a sample of e-cigarette users from the college population; and 3) Analyze the longitudinal EMA data using the innovative methodology for the following sub-aims: 3a) Validate two new e- cigarette consumption measures; 3b) Examine short-term subjective effects of naturally occurring simultaneous use of e-cigarettes and other substances including combustible cigarettes, alcohol, and marijuana; and 3c) Examine long-term effects of e-cigarette use patterns on initiation, progression and cessation of combustible cigarette, alcohol, and marijuana use; dependence symptomatology; respiratory health; and academic performance. This project will make significant impact on public health because the well- validated methodology and measurement will enable prevention scientists to better assess real-time, naturally occurring e-cigarette and polysubstance use patterns as well as their short-term and long-term effects. The results of the longitudinal EMA study will also provide guidance for designing and delivering more targeted prevention and intervention among college students who are involved in e-cigarette and polysubstance use. Furthermore, the proposed work is highly innovative because (i) the proposed statistical methods that can handle not only the conventional design but also the two modern designs of EMA studies are novel in both the statistical and behavioral science literature, and are tailor-made to be useful in research on tobacco and nicotine use; (ii) this project will provide new software to allow prevention scientists, for the first time, to effectively study substance use patterns and their long-term effects; (iii) the proposed innovative real-time and retrospective measures of e-cigarette consumption are based on both quantitative and qualitative data in our pilot study and can be applied to future EMA studies as well as conventional longitudinal studies; and (iv) the proposed longitudinal EMA study and future applications of the innovative methodology and measurement will produce new scientific knowledge in the substance abuse field that would be impossible to obtain using currently available statistical methods or measurement for e-cigarette consumption.